Group I feline coronavirus (FCoV) infections are common in cats usually cause only mild and often inapparent enteritis; in these cases the virus is classified as feline enteric coronavirus (FECV) (de Groot-Mijnes, J. D., et al., (2005) J Virol 79, 1036-1044; Haijema et al., 2007). However, feline infectious peritonitis (FIP) is a highly lethal systemic infection of cats caused by an FCoV classified as Feline infectious peritonitis virus (FIPV) (Haijema, et al. (2007) Molecular and Cellular Biology. Caister Academic Press, Norfolk, UK, pp. 183-203; Olsen, (1993) Vet Microbiol Vol. 36, pp. 1-37). There is currently no treatment available for FIP.
FCoVs exist as two major serotypes, with both type I and type II having the capacity to make the switch from FECV to FIPV. The prevalence of type I and type II within the cat population can vary; type I is the most prevalent, with type II viruses accounting for anywhere between 5 and 30% of viruses isolated. Like all known coronaviruses (CoV), both FIPV and FECV have a distinctive set of club-shaped spikes on their envelope, the spikes being comprised of the viral spike protein (S). The S protein is involved in determining the distinct cellular tropisms exhibited by FIPV and FECV (Rottier, P. J., et al. (2005) J Virol 79, 14122-14130), but the etiology of FIP and the role of S protein in it is not currently understood. It is known that cysteine protease mediated cleavage of coronavirus proteins, including cleavage of the S protein of some coronaviruses, is involved in the infection and replication processes of CoV. For example, U.S. patent application no. 2007/0203073 includes an analysis of the specificity of endosomal cysteine proteases in mediating SARS-CoV infection and cleavage of SARS-CoV S protein and found that the cysteine protease cathepsin L, but not cathepsin B, plays a critical role in SARS-CoV S protein-mediated viral entry. Other researchers (Collins, et al. (1991) Antimicrobial Agents And Chemotherapy, Vol. 35, pp 2444-2446) have determined that cystatin C, which is a potent inhibitor of cathepsin B, inhibited replication of a human coronaviruses, but not a murine coronavirus (A59). It was indicated that the lack of inhibition of murine coronavirus by cystatin C could be because, like FIPV, A59 murine CoV spreads via fusion with the plasma membranes of uninfected cells. It was also suggested that this could explain the observation that leupeptin, a serine and cysteine protease inhibitor, inhibits human coronavirus, but does not strongly inhibit A59 murine coronavirus or FIPV (Collins, et al. (1991). Thus, given the uncertainty about the molecular details of FCoV infection and replication, and the lack of any available FIP treatment, there is an ongoing need to develop methods for prophylaxis and/or treatment of FIP.